Cone-rod dystrophy 11

Summary

Cone-rod dystrophy 11 (MONDO:0012483) is a disease caused by RAX2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RAX2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 74

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 11
Mondo ID	MONDO:0012483
MeSH	C563671
OMIM	610381
DOID	DOID:0111018
UMLS	C1835865
MedGen	322767
GARD	0015484
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 11 · cone-rod dystrophy caused by mutation in RAX2 · cone-rod dystrophy type 11 · CORD11 · RAX2 cone-rod dystrophy

Data availability: 74 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › cone-rod dystrophy › cone-rod dystrophy 11

Related subtypes (27): cone-rod dystrophy 2, macular degeneration, X-linked atrophic, cone-rod dystrophy 1, cone-rod dystrophy 5, cone-rod dystrophy 6, cone dystrophy 3, cone-rod dystrophy 7, cone-rod dystrophy 3, Leber congenital amaurosis 4, cone-rod dystrophy 8, Newfoundland cone-rod dystrophy, cone-rod dystrophy 13, cone-rod dystrophy 10, retinal cone dystrophy 4, cone-rod dystrophy 12, cone-rod dystrophy 9, cone-rod dystrophy 15, cone-rod dystrophy 16, cone-rod dystrophy 17, cone-rod dystrophy 18, cone-rod dystrophy 19, cone-rod dystrophy 20, cone-rod dystrophy 21, X-linked cone-rod dystrophy, cone-rod dystrophy 22, cone-rod dystrophy 14, cone-rod dystrophy 24

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

74 retrieved; paginated sample, class counts are floors:

38 uncertain significance, 14 benign, 10 benign/likely benign, 9 conflicting classifications of pathogenicity, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1241	NM_001319074.4(RAX2):c.409G>C (p.Gly137Arg)	RAX2	Pathogenic	no assertion criteria provided
208124	NM_001319074.4(RAX2):c.465_475del (p.Ala156fs)	RAX2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3236193	NM_001319074.4(RAX2):c.443dup (p.His149fs)	RAX2	Pathogenic	criteria provided, single submitter
1242	NM_001319074.4(RAX2):c.411CCCGGG[3] (p.138PG[3])	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
262101	NM_001319074.4(RAX2):c.432G>A (p.Ala144=)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328967	NM_001319074.4(RAX2):c.217-8C>A	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328969	NM_001319074.4(RAX2):c.156G>A (p.Pro52=)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328971	NM_001319074.4(RAX2):c.76A>C (p.Lys26Gln)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
328972	NM_001319074.4(RAX2):c.19G>A (p.Glu7Lys)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889123	NM_001319074.4(RAX2):c.385G>A (p.Val129Met)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889200	NM_001319074.4(RAX2):c.49G>C (p.Gly17Arg)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
892560	NM_001319074.4(RAX2):c.131G>A (p.Arg44Gln)	RAX2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3249119	NM_001319074.4(RAX2):c.116T>C (p.Leu39Pro)	RAX2	Uncertain significance	criteria provided, single submitter
328940	NM_001319074.4(RAX2):c.*1523T>C	RAX2	Uncertain significance	criteria provided, single submitter
328941	NM_001319074.4(RAX2):c.*1483C>T	RAX2	Uncertain significance	criteria provided, single submitter
328949	NM_001319074.4(RAX2):c.*972T>A	RAX2	Uncertain significance	criteria provided, single submitter
328950	NM_001319074.4(RAX2):c.*949C>T	RAX2	Uncertain significance	criteria provided, single submitter
328959	NM_001319074.4(RAX2):c.*624G>A	RAX2	Uncertain significance	criteria provided, single submitter
328963	NM_001319074.4(RAX2):c.*88C>T	RAX2	Uncertain significance	criteria provided, single submitter
328965	NM_001319074.4(RAX2):c.*7C>T	RAX2	Uncertain significance	criteria provided, single submitter
328970	NM_001319074.4(RAX2):c.83G>A (p.Arg28Gln)	RAX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
328973	NM_001319074.4(RAX2):c.-269+8C>T	RAX2	Uncertain significance	criteria provided, single submitter
328976	NM_001319074.4(RAX2):c.-286G>T	RAX2	Uncertain significance	criteria provided, single submitter
328978	NM_001319074.4(RAX2):c.-319C>A	RAX2	Uncertain significance	criteria provided, single submitter
3892258	NM_001319074.4(RAX2):c.537G>C (p.Arg179Ser)	RAX2	Uncertain significance	criteria provided, single submitter
599132	NM_001319074.4(RAX2):c.275C>T (p.Ser92Leu)	RAX2	Uncertain significance	criteria provided, multiple submitters, no conflicts
635426	NM_001319074.4(RAX2):c.92G>A (p.Arg31His)	RAX2	Uncertain significance	criteria provided, single submitter
888997	NM_001319074.4(RAX2):c.*918G>A	RAX2	Uncertain significance	criteria provided, single submitter
888998	NM_001319074.4(RAX2):c.*897C>T	RAX2	Uncertain significance	criteria provided, single submitter
889062	NM_001319074.4(RAX2):c.*552C>T	RAX2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RAX2	Strong	Autosomal dominant	cone-rod dystrophy 11	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAX2	Orphanet:1872	Cone rod dystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RAX2	HGNC:18286	ENSG00000173976	Q96IS3	Retina and anterior neural fold homeobox protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAX2	Retina and anterior neural fold homeobox protein 2	May be involved in modulating the expression of photoreceptor specific genes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAX2	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
tendon of biceps brachii	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAX2	39	tissue_specific	marker	tendon of biceps brachii, buccal mucosa cell, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAX2	754

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RAX2	Q96IS3	71.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
visual perception	1	79.5×	0.038	RAX2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.086	RAX2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	RAX2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAX2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RAX2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RAX2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.